Fig. 3. UBP310 normalizes the spontaneous firing activity of SNc DA neurons of the parkinQ311X mouse.

a Examples of patch-clamp whole-cell recordings in current-clamp mode from an SNc DA neuron in an acute slice of ventral midbrain. The upper traces show membrane potential hyperpolarizing and depolarizing responses to intracellular injection of negative and positive current steps, respectively (±200 pA, 500 ms, lower traces). Note the relatively depolarized resting-membrane potential (−49 mV) and the prominent I_h-dependent depolarizing “sag” (arrow) typical of DA neurons. b Cell-attached recordings of spontaneous action potential (AP) firing of SNc DA neurons from WT and parkinQ311X mice at 25 days of age. The dot plot on the right shows the quantification of spontaneous firing frequencies. The mean firing frequency of the SNc DA neurons was significantly higher in parkinQ311X mice compared to WT mice (mean ± SEM WT: 1.75 ± 0.18 Hz, parkinQ311X mice: 2.96 ± 0.23 Hz). Data were obtained from 6 WT mice (16 recorded neurons) and 8 parkinQ311X mice (36 recorded neurons). Unpaired Student t test with Welch correction, ***p = 0.0001, t = 4.148, df = 47.75. c Summary dot plots showing spontaneous firing frequencies of SNc DA neurons in acute slices of ventral midbrain prepared from WT and parkinQ311X mice at 25 days of age upon extracellular perfusion with UBP310 (5 and 10 µM) and subsequent washout. Mean ± SEM, WT ACSF 2.3 ± 0.46 Hz, WT treated with UBP310 5 µM 2.03 ± 0.37 Hz, WT treated with UBP310 10 µM 1.85 ± 0.32 Hz, WT washout 1.96 ± 0.31 Hz; *p = 0.02, F = 7.83, Friedman repeated-measure ANOVA on ranks. Q311X ACSF 3.4 ± 0.5 Hz, Q311X treated with UBP310 5 µM 2.61 ± 0.36 Hz, Q311X treated with UBP310 10 µM 2.46 ± 0.41 Hz, Q311X washout 3.0 ± 0.55 Hz; one-way repeated-measure ANOVA Holm–Sidak test **p = 0.009, F = 11.87 (7 recorded neurons for each condition).